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TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
Author(s) -
Bullock Martyn,
Ren Yan,
O'Neill Christine,
Gill Anthony,
Aniss Adam,
Sywak Mark,
Sidhu Stan,
Delbridge Leigh,
Learoyd Diana,
Vathaire Florent,
Robinson Bruce G.,
CliftonBligh Roderick J.
Publication year - 2016
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12999
Subject(s) - medicine , proportional hazards model , papillary thyroid cancer , mutation , gastroenterology , retrospective cohort study , sanger sequencing , univariate analysis , endocrinology , thyroid carcinoma , thyroid , biology , oncology , gene , multivariate analysis , genetics
Summary Context TERT promoter mutations have been associated with adverse prognosis in papillary thyroid carcinomas ( PTC s). Objective We investigated the association between TERT promoter mutations and survival from PTC . Design Retrospective observational cohort study. Patients Eighty consecutive patients with PTC who underwent surgery between 1990 and 2003. Measurements TERT promoter was genotyped in DNA from 80 archival PTC s by Sanger sequencing. Median follow‐up was 106 months (range 1–270). Outcomes analysis was stratified according to disease and overall survival status. For each parameter, relative risk ( RR ) adjusted for age at first surgery and gender was estimated. Both univariate and multivariate analyses were performed using logistic regression, Kaplan–Meier survival analysis and Cox regression models. Results PTC s from 11 patients (14%) contained either C228T or C250T TERT promoter mutation. TERT mutations were significantly associated with adverse prognostic features such as older age ( P = 0·002), male gender ( P = 0·01) and Stage IV disease ( P = 0·03). Four patients died from PTC during follow‐up: 3 patients with TERT mutations (27%) and one without (1·5%). Disease‐related mortality rate with or without TERT mutations was 33·7 vs 1·6 per 1000 patient‐years respectively, that is 10 (95% CI = 1·0–104·1, P = 0·05) fold higher, after adjustment for age at first surgery and gender. The combination of TERT promoter mutation and BRAF V600E significantly increased disease‐related death risk ( P = 0·002). TERT mutations increased expression of a reporter gene in thyroid cells containing BRAF V600E . Conclusions TERT promoter mutations are a major indicator of death due to PTC s. Conversely, absence of TERT mutations portends better survival.